AstraZeneca upbeat on approvals in China and the US

(Sharecast News) - AstraZeneca announced on Monday that budesonide/glycopyrronium/formoterol fumarate has been approved in China for the maintenance treatment of chronic obstructive pulmonary disease (COPD).
At the same time, the FTSE 100 pharmaceuticals giant, alongside Daiichi Sankyo, said that the US Food and Drug Administration (FDA) has approved 'Enhertu' - fam-trastuzumab deruxtecan-nxki - for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer, who had received two or more prior anti-HER2 based regimens in the metastatic setting.

For the approval of budesonide/glycopyrronium/formoterol fumarate in China, AstraZeneca said it was the first approval by the National Medical Products Administration for a triple-combination therapy in a pressurised metered-dose inhaler (pMDI), using its 'Aerosphere' delivery technology.

The approval followed a priority review, and was based on results from the phase 3 'KRONOS' trial, in which PT010 demonstrated a "statistically significant improvement" in trough-forced expiratory volume in one second - the primary endpoint for China - compared with dual-combination therapies 'Bevespi Aerosphere' - glycopyrronium/formoterol fumarate - and 'PT009' - budesonide/formoterol fumarate.

It said the safety and tolerability of PT010 was consistent with the known profiles of the dual comparators.

Data from the KRONOS trial was published in The Lancet Respiratory Medicine in October 2018.

"Chronic obstructive pulmonary disease affects almost 100 million people in China, and is a leading cause of morbidity and mortality," said AstraZeneca's executive vice-president of biopharmaceuticals research and development, Mene Pangalos.

"With this approval, we are now able to provide a powerful new triple-combination therapy to patients for whom new treatments are critically needed.

"Our triple-combination therapy is administered in a pressurised metered-dose inhaler, an important device option for clinicians and patients in China."

Professor Wang Chen, director of the China National Clinical Research Centre for Respiratory Diseases, director of the Centre for Respiratory Disease at China-Japan Friendship Hospital, and China national lead investigator of the KRONOS trial, added that addressing the burden of chronic obstructive pulmonary disease in China was a public health priority.

"Triple-combination therapy will play an important role in helping patients manage their disease.

"In the KRONOS trial, budesonide/glycopyrronium/formoterol fumarate provided rapid and sustained lung function improvements in patients with moderate-to-very-severe disease."

Budesonide/glycopyrronium/formoterol fumarate was approved in Japan in June as 'Breztri Aerosphere' - a triple-combination therapy to relieve symptoms of COPD.

The medicine is also under regulatory review in the United States and the European Union, under the name PT010.

On the approval of 'Enhertu' in the US, AstraZeneca said the indication was approved under the 'Accelerated Approval' programme, based on tumour response rate and duration of response.

Continued approval for the indication could be contingent on verification and description of clinical benefit in a confirmatory trial.

Enhertu is a HER2-directed antibody-drug conjugate (ADC), with the FDA approval being based on the results of the registrational phase 2 trial 'DESTINY-Breast01' of Enhertu monotherapy at 5.4mg per kilogram, in patients with HER2-positive metastatic breast cancer.

All patients received prior trastuzumab, trastuzumab emtansine and 66% had prior pertuzumab.

The company said the phase 2 trial results showed a confirmed objective response rate of 60.3%, including a 4.3% complete response rate and a 56.0% partial response rate.

A median duration of response of 14.8 months) was demonstrated as of 1 August.

In addition, a median progression-free survival of 16.4 months, based on a median duration of follow up of 11.1 months, was recently presented at the San Antonio Breast Cancer Symposium and published online in The New England Journal of Medicine.

"Enhertu has shown impressive results in women with HER2-positive metastatic breast cancer, with the majority of women benefiting from treatment and the median duration of the response exceeding 14 months," said AstraZeneca's executive vice-president of oncology research and development, José Baselga.

"With this first approval, we are proud to bring Enhertu to patients with high unmet need and we look forward to further exploring its potential in additional settings."

Antoine Yver, executive vice-president and global head of oncology research and development at Daiichi Sankyo, added that the approval of Enhertu underscored that the specifically engineered HER2-directed antibody-drug conjugate was delivering on its intent to establish an important new treatment for patients with HER2-positive metastatic breast cancer.

"Since the beginning of our clinical trial programme four years ago, we have focused on the opportunity to transform the treatment landscape for patients with HER2-positive metastatic breast cancer, and we are extremely proud of how quickly we delivered Enhertu to patients in the US, as Enhertu represents one of the fastest-developed biologics in oncology."

AstraZeneca and Daiichi Sankyo said the safety of Enhertu was evaluated in a pooled analysis from both the phase 2 trial 'DESTINY-Breast01', and the earlier phase 1 trial, among a total of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of Enhertu at 5.4 mg per kilogram.

The most common adverse reactions were nausea, fatigue, vomiting, alopecia and constipation.

Interstitial lung disease or pneumonitis occurred in 9% of patients, with fatal outcomes due to that occurring in six patients.

Following an initial interstitial lung disease (ILD) management programme already in place, a further monitoring, management and educational campaign on ILD and pneumonitis was launched in 2019.

A regulatory submission for the treatment of patients with HER2-positive metastatic breast cancer had also been made to Japan's Ministry of Health, Labour and Welfare based on the 'DESTINY-Breast01' and phase 1 trials.

AstraZeneca and Daiichi Sankyo said they were also exploring the further potential of Enhertu in HER2-breast cancer, with three ongoing phase 3 trials.